artikel kelainan kulit - vitiligo dll

7/28/2019 Artikel Kelainan Kulit - Vitiligo Dll

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VitiligoIntroductionBackground

Vitiligo is an acquired pigmentary disorder of the skin and mucousmembranes, and it is characterized by circumscribed depigmentedmacules and patches. It is a progressive disorder in which some or all ofthe melanocytes in the affected skin are selectively destroyed. Vitiligoaffects 0.5-2% of the world population, and the average age of onset is 20years.

PathophysiologyVitiligo is a multifactorial polygenic disorder with a complex pathogenesis.It is related to both genetic and nongenetic factors. Although severaltheories have been proposed about the pathogenesis of vitiligo, theprecise cause remains unknown. Generally agreed upon principles are an

absence of functional melanocytes in vitiligo skin and a loss ofhistochemically recognized melanocytes, owing to their destruction.However, the destruction is most likely a slow process resulting in aprogressive decrease of melanocytes. Theories regarding destruction ofmelanocytes include autoimmune mechanisms,1cytotoxic mechanisms, anintrinsic defect of melanocytes, oxidant-antioxidant mechanisms, andneural mechanisms.Autoimmune destruction of melanocytesThe autoimmune theory proposes alteration in humoral and cellularimmunity in the destruction of melanocytes of vitiligo. Thyroid disorders,

particularly Hashimoto thyroiditis and Graves disease; otherendocrinopathies, such as Addison disease and diabetes mellitus; andalopecia areata; pernicious anemia; inflammatory bowel disease;psoriasis; and autoimmune polyglandular syndrome are all associatedwith vitiligo. The most convincing evidence of an autoimmunepathogenesis is the presence of circulating antibodies in patients withvitiligo.2The role of humoral immunity is further supported by theobservation that melanocytes are destroyed in healthy skin engraftedonto nude mice injected with vitiligo patient sera.3

In addition to the involvement of humoral immune mechanisms in thepathogenesis of vitiligo, strong evidence indicates involvement of cellular

immunity in vitiligo. Destruction of melanocytes may be directly mediatedby autoreactive CD8+ T cells. Activated CD8+ T cells have beendemonstrated in perilesional vitiligo skin. In addition, melanocyte-specificT cells have been detected in peripheral blood of patients withautoimmune vitiligo.4

The following related eMedicine articles may be of interest: Hashimoto Thyroiditis Graves Disease Addison Disease Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2

Alopecia Areata Pernicious Anemia
http://emedicine.medscape.com/article/120937-overviewhttp://emedicine.medscape.com/article/120619-overviewhttp://emedicine.medscape.com/article/116467-overviewhttp://emedicine.medscape.com/article/117739-overviewhttp://emedicine.medscape.com/article/117853-overviewhttp://emedicine.medscape.com/article/1069931-overviewhttp://emedicine.medscape.com/article/204930-overviewhttp://emedicine.medscape.com/article/120937-overviewhttp://emedicine.medscape.com/article/120619-overviewhttp://emedicine.medscape.com/article/116467-overviewhttp://emedicine.medscape.com/article/117739-overviewhttp://emedicine.medscape.com/article/117853-overviewhttp://emedicine.medscape.com/article/1069931-overviewhttp://emedicine.medscape.com/article/204930-overview


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Inflammatory Bowel Disease Psoriasis Autoimmune Polyglandular Syndrome, Type 1

Additionally, for a Medscape CME course related to autoimmunity andmedications, see Drug Insight: Autoimmune Effects of Medications: What's

New?.

Intrinsic defect of melanocytesVitiligo melanocytes may have an intrinsic defect leading to melanocytedeath. These melanocytes demonstrate various abnormalities, includingabnormal, rough endoplasmic reticulum and incompetent synthesis andprocessing of melanocytes. In addition, homing-receptor dysregulationhas also been detected. Early apoptosis of melanocytes has also beensuggested as a cause of reduced melanocyte survival; however,subsequent investigation found that the relative apoptosis susceptibility ofvitiligo melanocytes was comparable with that of normal control pigment

cells.5

Disturbance in oxidant-antioxidant system in vitiligo

Oxidant stress may also play an essential role in the pathogenesis ofvitiligo. Studies suggest that accumulation of free radicals toxic tomelanocytes leads to their destruction. Because patients with vitiligoexhibit a characteristic yellow/green or bluish fluorescence in clinicallyaffected skin, this led to the discovery that the fluorescence is due toaccumulation of 2 different oxidized pteridines. The overproduction of

pteridines led to the discovery of a metabolic defect in tetrahydrobiopterinhomeostasis in patients with vitiligo, which results in the accumulation ofmelanocytotoxic hydrogen peroxide.6

Neural theory

Case reports describe patients afflicted with a nerve injury who also havevitiligo have hypopigmentation or depigmentation in denervated areas.Additionally, segmental vitiligo frequently occurs in a dermatomal pattern,which suggests that certain chemical mediators are released from nerveendings that affect melanin production. Further, sweating and

vasoconstriction are increased in depigmented patches of vitiligo,implying an increase in adrenergic activity. Finally, increased urinaryexcretion of homovanillic acid and vanilmandelic acid (neurometabolites)has been documented in patients with vitiligo. This may be a secondary orprimary phenomenon.7

In summary, although the ultimate cause of vitiligo is not completelyknown, this condition does not reflect simple melanocyte loss, butpossible immunologic alterations and other molecular defects leading topigment cell destruction; however, melanocytes may be present indepigmented skin after years of onset and may still respond to medicaltherapy under appropriate stimulation.
http://emedicine.medscape.com/article/179037-overviewhttp://emedicine.medscape.com/article/762805-overviewhttp://emedicine.medscape.com/article/124183-overviewhttp://www.medscape.com/viewarticle/568595http://www.medscape.com/viewarticle/568595http://emedicine.medscape.com/article/179037-overviewhttp://emedicine.medscape.com/article/762805-overviewhttp://emedicine.medscape.com/article/124183-overviewhttp://www.medscape.com/viewarticle/568595http://www.medscape.com/viewarticle/568595


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Genetics of vitiligo8

Vitiligo is characterized by incomplete penetrance, multiple susceptibilityloci, and genetic heterogeneity. The inheritance of vitiligo may involvegenes associated with the biosynthesis of melanin, a response to

oxidative stress, and regulation of autoimmunity.9Human leukocyte antigens (HLAs) may be associated, but not in aconsistent manner. For example, HLA-DR4 is increased in blacks, HLA-B13is increased in Moroccan Jews, and HLA-B35 is increased in Yemenite Jews.An association with HLA-B13 is described in the presence of antithyroidantibodies.

FrequencyUnited States

In the United States, the relative rate is 1%.International

Vitiligo is relatively common, with a rate of 1-2%. Approximately 30% ofcases occur with a familial clustering of cases.

SexA female preponderance has been reported, but it is not statisticallysignificant and the discrepancy has been attributed to an increase inreporting of cosmetic concerns by female patients.

AgeVitiligo may appear at any time from birth to senescence, although theonset is most commonly observed in persons aged 10-30 years.

It rarely is seen in infancy or old age. Nearly all cases of vitiligo areacquired relatively early in life.

The average age of onset is approximately 20 years. The age of onset isunlikely to vary between the sexes.

Heightened concern about the appearance of the skin may contribute toan early awareness of the condition among females.

ClinicalHistoryThe most common form of vitiligo is an amelanotic macule or patchsurrounded by healthy skin. The macules are chalk or milk-white in color,and lesions are well demarcated.The lesions are not readily apparent in lightly pigmented individuals;

however, they are easily distinguishable with a Wood lamp examination.PhysicalVitiligo manifests as acquired white or hypopigmented macules orpatches. The lesions are usually well demarcated, and they are round,oval, or linear in shape. The borders may be convex.6Lesions enlargecentrifugally over time at an unpredictable rate. Lesions range frommillimeters to centimeters in size. Initial lesions occur most frequently onthe hands, forearms, feet, and face, favoring a perioral and perioculardistribution.Vitiligo lesions may be localized or generalized, with the latter being morecommon than the former. Localized vitiligo is restricted to one generalarea with a segmental or quasidermatomal distribution. Generalizedvitiligo implies more than one general area of involvement. In this


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situation, the macules are usually found on both sides of the trunk, eithersymmetrically or asymmetrically arrayed.The most common sites of involvement are the face, neck, and scalp.Many of the most common sites of occurrence are areas subjected torepeated trauma, including the following:

Bony prominences Extensor forearm Ventral wrists Dorsal hands Digital phalanges

Involvement of the mucous membranes is frequently observed in thesetting of generalized vitiligo. Vitiligo often occurs around body orificessuch as the lips, genitals, gingiva, areolas, and nipples.Body hair (leukotrichia) in vitiliginous macules may be depigmented.Vitiligo of the scalp usually appears as a localized patch of white or grayhair, but total depigmentation of all scalp hair may occur. Scalp

involvement is the most frequent, followed by involvement of theeyebrows, pubic hair, and axillary hair, respectively. Leukotrichia mayindicate a poor prognosis in regard to repigmentation. Spontaneousrepigmentation of depigmented hair in vitiligo does not occur.Clinical variantsTrichrome vitiligo has an intermediate zone of hypochromia locatedbetween the achromic center and the peripheral unaffected skin. Thenatural evolution of the hypopigmented areas is progression to fulldepigmentation. This results in 3 shades of colorbrown, tan, and whitein the same patient (see Media File 1).Marginal inflammatory vitiligo results in a red, raised border, which ispresent from the onset of vitiligo (in rare cases) or which may appearseveral months or years after the initial onset. A mild pruritus may bepresent (see Media File 2).Quadrichrome vitiligo is another variant of vitiligo, which reflects thepresence of a fourth color (ie, dark brown) at sites of perifollicularrepigmentation. A case of pentachrome vitiligo with 5 shades of color hasalso been described.7

Blue vitiligo results in blue coloration of vitiligo macules. This type hasbeen observed in a patient with postinflammatory hyperpigmentation whothen developed vitiligo.

Koebner phenomenon is defined as the development of vitiligo in sites ofspecific trauma, such as a cut, burn, or abrasion. Minimum injury isrequired for Koebner phenomenon to occur.Clinical classifications of vitiligoThe classification system is important because of the special significanceassigned by some authorities to each type of vitiligo. The most widelyused classification of vitiligo is localized, generalized, and universal typesand is based on the distribution, as follows:

Localizedo Focal: This type is characterized by one or more macules in one

area, most commonly in the distribution of the trigeminal nerve.o Segmental: This type manifests as one or more macules in a

dermatomal or quasidermatomal pattern. It occurs most commonly
http://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1068962-media


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in children. More than half the patients with segmental vitiligo havepatches of white hair or poliosis. This type of vitiligo is notassociated with thyroid or other autoimmune disorders.

o Mucosal: Mucous membranes alone are affected. Generalized

o

Acrofacial: Depigmentation occurs on the distal fingers andperiorificial areas.o Vulgaris: This is characterized by scattered patches that are widely

distributed.o Mixed: Acrofacial and vulgaris vitiligo occur in combination, or

segmental and acrofacial vitiligo and/or vulgaris involvement arenoted in combination.

Universal: This is complete or nearly complete depigmentation. It is oftenassociated with multiple endocrinopathy syndrome.

Classification by progression, prognosis, and treatmentWhen progression, prognosis, and treatment are considered, vitiligo canbe classified into 2 major clinical types: segmental and nonsegmental.

Segmental: This usually has an onset early in life and rapidly spreads inthe affected area. The course of segmental vitiligo can arrest, anddepigmented patches can persist unchanged for the life of the patient (seeMedia File 3).

Nonsegmental: This type includes all types of vitiligo, except segmentalvitiligo (see Media File 4).10

CausesTheories regarding destruction of melanocytes include autoimmunemechanisms, cytotoxic mechanisms, intrinsic melanocyte defects,oxidant-antioxidant mechanisms, and neural mechanisms.

Autoimmune and cytotoxic hypotheses: Aberration of immune surveillanceresults in melanocyte dysfunction or destruction.

Neural hypothesis: A neurochemical mediator destroys melanocytes orinhibits melanin production.

Oxidant-antioxidant mechanisms: An intermediate or metabolic product ofmelanin synthesis causes melanocyte destruction.

Intrinsic defect of melanocytes: Melanocytes have an inherent abnormalitythat impedes their growth and differentiation in conditions that supportnormal melanocytes.

Because none of these theories alone is entirely satisfactory, some havesuggested a composite hypothesis.

Differential DiagnosesAddison Disease Postinflammatorydepigmentation

Alezzandrini Syndrome Prior treatment withcorticosteroids

Chemical leukoderma SclerodermaHalo Nevus Tinea VersicolorIdiopathic GuttateHypomelanosis

Treponematosis

Leprosy Tuberous SclerosisMalignant Melanoma Vogt-Koyanagi-Harada

SyndromeNevus Anemicus Waardenburg Syndrome
http://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1096911-overviewhttp://emedicine.medscape.com/article/1117255-overviewhttp://emedicine.medscape.com/article/1057446-overviewhttp://emedicine.medscape.com/article/1091575-overviewhttp://emedicine.medscape.com/article/1068422-overviewhttp://emedicine.medscape.com/article/1068422-overviewhttp://emedicine.medscape.com/article/1104977-overviewhttp://emedicine.medscape.com/article/1112322-overviewhttp://emedicine.medscape.com/article/1100753-overviewhttp://emedicine.medscape.com/article/1118177-overviewhttp://emedicine.medscape.com/article/1118177-overviewhttp://emedicine.medscape.com/article/1084329-overviewhttp://emedicine.medscape.com/article/1113314-overviewhttp://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1068962-mediahttp://emedicine.medscape.com/article/1096911-overviewhttp://emedicine.medscape.com/article/1117255-overviewhttp://emedicine.medscape.com/article/1057446-overviewhttp://emedicine.medscape.com/article/1091575-overviewhttp://emedicine.medscape.com/article/1068422-overviewhttp://emedicine.medscape.com/article/1068422-overviewhttp://emedicine.medscape.com/article/1104977-overviewhttp://emedicine.medscape.com/article/1112322-overviewhttp://emedicine.medscape.com/article/1100753-overviewhttp://emedicine.medscape.com/article/1118177-overviewhttp://emedicine.medscape.com/article/1118177-overviewhttp://emedicine.medscape.com/article/1084329-overviewhttp://emedicine.medscape.com/article/1113314-overview


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Onchocerciasis (RiverBlindness)PiebaldismPityriasis Alba

Other Problems to Be Considered

Vitiligo and ocular diseaseThe uveal tract and retinal pigment epithelium contain pigment cells.Choroidal abnormalities have been reported in up to 30% of patients, andiritis has been reported in approximately 5% of patients. Exophthalmosmay occur in the setting of concomitant Graves disease. Uveitis is themost significant ocular abnormality associated with vitiligo. The mostsevere form of uveitis is seen in the Vogt-Koyanagi-Harada syndrome. Thissyndrome is characterized by vitiligo, uveitis, aseptic meningitis,dysacusis, tinnitus, poliosis, and alopecia.

Alezzandrini syndrome includes facial vitiligo, poliosis, deafness, andunilateral visual changes. The affected eye has decreased visual acuityand an atrophic iris.6

Although the color of the irides does not change in patients with vitiligo,depigmented areas in pigment epithelium and choroid occur in up to 40%of patients.

Vitiligo and autoimmune disordersVitiligo is frequently associated with disorders of autoimmune origin, withthyroid abnormalities being the most common. Vitiligo usually precedesthe onset of thyroid dysfunction. Patients with autoimmune

polyendocrinopathy candidiasis-ectodermal dystrophy have an increasedprevalence of vitiligo. In this genetic syndrome, autoantibodies causedestruction of endocrine cells.11

Moreover, studies suggest that an association exists between a positivefamily history of vitiligo, autoimmune/endocrine diseases, leukotrichia,and an increased incidence of vitiligo in children. In addition, pediatricpatients with a positive family history of vitiligo show an earlier age ofdisease onset.12

Vitiligo and auditory abnormalities13

Melanin may play a significant role in the establishment and/ormaintenance of the structure and function of the auditory system andmay modulate the transduction of the auditory stimuli by the inner ear.14

The membranous labyrinth of the inner ear contains melanocytes, and theheaviest pigmentation is present in the scala vestibuli. Because vitiligoaffects all melanocytes, auditory disturbances may result. Several studieshave described familial vitiligo associated with hearing abnormalities andhypoacusis in 16% of patients younger than 40 years who have vitiligo.14

Vitiligo and melanoma15,16

Vitiligolike depigmentation can occur in patients with malignantmelanoma and is believed to result from a T-cellmediated reaction to
http://emedicine.medscape.com/article/1109409-overviewhttp://emedicine.medscape.com/article/1109409-overviewhttp://emedicine.medscape.com/article/1113248-overviewhttp://emedicine.medscape.com/article/1068868-overviewhttp://emedicine.medscape.com/article/1109409-overviewhttp://emedicine.medscape.com/article/1109409-overviewhttp://emedicine.medscape.com/article/1113248-overviewhttp://emedicine.medscape.com/article/1068868-overview


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antigenic melanoma cells and cross-reactivity to healthy melanocytes.Most patients with melanoma or with vitiligo develop antibodies to similarantigens that are present both on melanocytes and on melanoma cells.These findings support the hypothesis that the clinical link between the 2diseases results from immune responses to antigens shared by normal

and malignant pigment cells. Studies have demonstrated that a halonevus, hypopigmentation, or depigmentation may occur in patients withmelanoma. The depigmentation or hypopigmentation spreadscentrifugally from the trunk to other parts of the body. The sites ofdepigmentation may be remote from the original site of melanoma.Although metastasis has most likely occurred in the majority of patients,active vitiligo in these patients may signal a longer survival time thanexpected.

WorkupLaboratory Studies

Although the diagnosis of vitiligo generally is made on the basis of clinicalfindings, biopsy is occasionally helpful for differentiating vitiligo fromother hypopigmentary disorders.Vitiligo may be associated with other autoimmune diseases, especiallythyroid disease and diabetes mellitus. Other associated autoimmunediseases include pernicious anemia, Addison disease, and alopecia areata.Patients should be made aware of signs and symptoms that suggest theonset of hypothyroidism, diabetes, or other autoimmune disease. If signsor symptoms occur, appropriate tests should be performed.16

Thyrotropin testing is the most cost-effective screening test forthyroid disease. Antinuclear antibody screening is also helpful. ACBC count with indices helps rule out anemia.

Clinicians should also consider investigating for serumantithyroglobulin and antithyroid peroxidase antibodies, particularlyif thyroid involvement is suspected. Antithyroid peroxidaseantibodies are regarded as a sensitive and specific marker ofautoimmune thyroid antibodies. Screening for diabetes can beaccomplished with fasting blood glucose or glycosylated hemoglobintesting.

Other TestsVitiligo is diagnosed by means of inspection with a Wood lamp.

Histologic FindingsMicroscopic examination of involved skin shows a complete absence ofmelanocytes in association with a total loss of epidermal pigmentation.Superficial perivascular and perifollicular lymphocytic infiltrates may beobserved at the margin of vitiliginous lesions, consistent with a cell-mediated process destroying melanocytes. Degenerative changes havebeen documented in keratinocytes and melanocytes in both the borderlesions and adjacent skin. Other documented changes include increasednumbers of Langerhans cells, epidermal vacuolization, and thickening ofthe basement membrane. Loss of pigment and melanocytes in theepidermis is highlighted by Fontana-Masson staining andimmunohistochemistry testing.17,18


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TreatmentMedical CareNo single therapy for vitiligo produces predictably good results in allpatients; the response to therapy is highly variable. Treatment must be

individualized, and patients should be made aware of the risks associatedwith therapy. During medical therapy, pigment cells arise and proliferatefrom the following 3 sources:

The pilosebaceous unit, which provides the highest number of cells,migrating from the external root sheath toward the epidermis

Spared epidermal melanocytes not affected during depigmentation19

The border of lesions, migrating up to 2-4 mm from the edge

Systemic phototherapySystemic phototherapy induces cosmetically satisfactory repigmentationin up to 70% of patients with early or localized disease.16

Narrow-band UV-B phototherapy is widely used and produces good clinicalresults. Narrow-band fluorescent tubes (Philips TL-01/100W) with anemission spectrum of 310-315 nm and a maximum wavelength of 311 nmare used. Treatment frequency is 2-3 times weekly, but never onconsecutive days. This treatment can be safely used in children, pregnantwomen, and lactating women. Short-term adverse effects include pruritusand xerosis. Several studies have demonstrated the effectiveness ofnarrow-band UV-B therapy as monotherapy.UV-B narrow-band microphototherapy20is therapy targeting the specificsmall lesions. Selective narrow-band UV-B (311 nm) is used with a fiberoptic system to direct radiation to specific areas of skin. Narrow-band UV-

B has become the first choice of therapy for adults and children withgeneralized vitiligo.Psoralen photochemotherapy involves the use of psoralens combined withUV-A light. Treatment with 8-methoxypsoralen, 5-methoxypsoralen, andtrimethylpsoralen plus UV-A (PUVA) has often been the most practicalchoice for treatment, especially in patients with skin types IV-VI who havewidespread vitiligo. Psoralens can be applied either topically or orally,followed by exposure to artificial UV light or natural sunlight. Vitiligo onthe back of the hands and feet is highly resistant to therapy.The best results from PUVA can be obtained on the face, trunk, and

proximal parts of the extremities. However, 2-3 treatments per week formany months are required before repigmentation from perifollicularopenings merges to produce confluent repigmentation. The total numberof PUVA treatments required is 50-300. Repigmentation occurs in aperifollicular pattern.The advantages of narrow-band UV-B over PUVA include shorter treatmenttimes, no drug costs, no adverse GI effects (eg, nausea), and no need forsubsequent photoprotection.Laser therapyAnother innovation is therapy with an excimer laser, which producesmonochromatic rays at 308 nm to treat limited, stable patches of vitiligo.

This new treatment is an efficacious, safe, and well-tolerated treatmentfor vitiligo when limited to less than 30% of the body surface. However,


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therapy is expensive. Localized lesions of vitiligo are treated twice weeklyfor an average of 24-48 sessions.According to studies from 2004 and 2007, combination treatment with0.1% tacrolimus ointment plus the 308-nm excimer laser is superior to308-nm excimer laser monotherapy for the treatment of UV-resistant

vitiliginous lesions.21,22Steroid therapySystemic steroids (prednisone) have been used, although prolonged useand their toxicity are undesirable.23Steroids have been reportedanecdotally to achieve success when given in pulse doses or low doses tominimize adverse effects. The benefits versus the toxicity of this therapymust be weighed carefully. More research is necessary to establish thesafety and effectiveness of this therapy for vitiligo.A topical steroid preparation is often chosen first to treat localized vitiligobecause it is easy and convenient for both doctors and patients tomaintain the treatment. The results of therapy have been reported asmoderately successful, particularly in patients with localized vitiligo and/oran inflammatory component to their vitiligo, even if the inflammation issubclinical.In general, intralesional corticosteroids should be avoided because of thepain associated with injection and the risk of cutaneous atrophy.Topical therapies

Topical tacrolimus ointment (0.03% or 0.1%) is an effective alternative therapy

for vitiligo, particularly when the disease involves the head and neck.

Combination treatment with topical tacrolimus 0.1% plus the 308-nm excimer

laser is superior to monotherapy with the 308-nm excimer laser monotherapy for

UV-resistant vitiliginous lesions. On the face, narrow-band UV-B works better ifcombined with pimecrolimus 1% cream rather than used alone.24,25

The combination of topical calcipotriene and narrow-band UV-B or PUVAresults in improvement appreciably better than that achieved withmonotherapy.Depigmentation therapyIf vitiligo is widespread and attempts at repigmentation do not producesatisfactory results, depigmentation may be attempted in selectedpatients.The long-term social and emotional consequences of depigmentationmust be considered. Depigmentation should not be attempted unless thepatient fully understands that the procedure generally results inpermanent depigmentation. Some authorities have recommendedconsultation with a mental health professional to discuss potential socialconsequences of depigmentation.A 20% cream of monobenzylether of hydroquinone is applied twice dailyfor 3-12 months. Burning or itching may occur. Allergic contact dermatitismay be seen.26

Topical PUVA is of benefit in some patients with localized lesions. Creamand solution of 8-methoxypsoralen (0.1-0.3% concentration) are availablefor this treatment.6It is applied 30 minutes prior to UV-A radiation (usually

0.1-0.3 J/cm2

UV-A) exposure. It should be applied once or twice a week.Physicians who prescribe PUVA therapy should be thoroughly familiar with


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the risks associated with the treatment. Additional UV-A exposure shouldbe avoided while skin is sensitized because severe burns may occur ifpatients receive additional UV-A exposure. Sunscreens should be given toall patients with vitiligo to minimize risk of sunburn or repeated solardamage to depigmented skin. Patients must understand that most

sunblocks have a limited ability to screen UV-A light.Of general concern, tanning of surrounding normal skin exaggerates theappearance of vitiligo, and this is prevented by sun protection.Sunscreens with a sun protection factor of 15 or higher are best.

Surgical CareSurgical alternatives exist for the treatment of vitiligo; however, becauseof the time-consuming nature of surgical therapies, these treatmentregimens are limited to segmental or localized vitiligo. Unilateral(segmental) vitiligo has been shown as the most stable form, respondingwell to surgical interventions in numerous studies. Such areas as dorsal

fingers, ankles, forehead, and hairline tend to not repigment well. Patientswho have small areas of vitiligo with stable activity are candidates forsurgical transplants. The most important factors indicating stability are asfollows:

No progression of lesions for at least 2 years Spontaneous repigmentation indicates vitiligo inactivity A positive minigrafting test disclosing repigmentation at 4-5 minigrafts,

which, to date, is the most accurate evidence of vitiligo stability Absence of new koebnerization, including the donor site for the

minigrafting test Unilateral vitiligo most stable form of vitiligo27

Five basic methods for repigmentation surgery have been described, asfollows28,29:

Noncultured epidermal suspensions: After the achromic epidermis isremoved, an epidermal suspension with melanocytes and keratinocytespreviously prepared by trypsinization of normally pigmented donor skin isspread onto the denuded area and immediately covered with nonadherentdressings.

Thin dermoepidermal grafts: The depigmented epidermis is removed bysuperficial dermabrasion, including the papillary dermis, and very thindermoepidermal sheets harvested with dermatome are grafted onto thedenuded skin.

Suction epidermal grafting: Epidermal grafts can be obtained by vacuum

suction, usually with 150 mm Hg. The recipient site can be prepared bysuction, freezing, or dermabrasion of the sites 24 hours before grafting.

The depigmented blister roof is discarded, and the epidermal donor graftis placed on the vitiliginous areas.

Punch minigrafting: Small donor grafts are inserted into the incision ofrecipient sites and held in place by a pressure dressing. The graft healsreadily and begins to show repigmentation within 4-6 weeks. Somepebbling persists but is minimal, and the cosmetic result is excellent.

Cultured epidermis with melanocytes or cultured melanocyte suspensions:Depigmented skin is removed using liquid nitrogen, superficialdermabrasion, thermosurgery, or carbon dioxide lasers; very thin sheets ofcultured epidermis are grafted or suspensions are spread onto thedenuded surface.27


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Micropigmentation30is another option. Tattooing can be used to repigmentdepigmented skin in dark-skinned individuals. Color matching is difficult,and the color tends to fade. Skin can be dyed with dihydroxyacetonepreparations, although the color match is often poor.

Consultations

Consultation with an ophthalmologist is warranted. Additionally,psychological needs must be addressed on a continual basis withappropriate referrals to mental health specialists.7

MedicationThe goals of pharmacotherapy are to reduce morbidity and to preventcomplications.

CorticosteroidsCorticosteroids have anti-inflammatory properties and cause profound andvaried metabolic effects. In addition, these agents modify the body'simmune response to diverse stimuli. These drugs are used to stop spread

of vitiligo and accomplish repigmentation. Data supporting the efficacy ofsuch treatment is largely anecdotal. More study is needed to establish thesafety and efficacy of systemic agents.

Topical steroids: triamcinolone 0.1% ointment or cream (Aristocort),

hydrocortisone 2.5 % ointment, clobetasol ointment or cream

(Clobex)

For inflammatory dermatosis responsive to steroids; decreasesinflammation by suppressing migration of polymorphonuclear leukocytesand reversing capillary permeability. Intramuscular injection may be used

for widespread skin disorder, or intralesional injections may be used forlocalized skin disorder. Moderately high potency; available as ointment(0.1%) or cream (0.5%).Adult

Apply a thin film qd; more frequent applications may be required,especially in areas where preparation tends to be removed beforeabsorption is completePediatric

Apply as in adultsCoadministration with barbiturates, phenytoin, and rifampin decreaseseffects of triamcinolone

Documented hypersensitivity; fungal, viral, and bacterial skin infectionsPregnancy

C - Fetal risk revealed in studies in animals but not established or notstudied in humans; may use if benefits outweigh risk to fetusPrecautions

Do not use in decreased skin circulation; prolonged use, applications overlarge areas, and use of potent steroids and occlusive dressings may resultin systemic absorption; systemic absorption may cause Cushingsyndrome, reversible HPA axis suppression, hyperglycemia, andglycosuria

Psoralens


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These agents are used with UV-A exposure for the treatment of localizedor generalized vitiligo.

Methoxsalen (8-MOP, Oxsoralen)

Inhibits mitosis by covalently binding to pyrimidine bases in DNA when

photoactivated by UV-A. Effective in treating hyperkeratosis.Adult

PO: 0.3-0.4 mg/kg PO with food 1.5 h before UV-A exposure once or twiceweekly; alternatively, 0.57 mg/kg 1.5-2 h before UV exposure; at least 48h apartTopically: 0.1% ointment; apply 30 min before controlled UV-A exposureonce or twice weeklyPediatric

12 years: Administer as in adults

Toxicity increases with phenothiazines, griseofulvin, nalidixic acid,tetracyclines, thiazides, and sulfanilamideDocumented hypersensitivity; squamous cell cancer; cataracts; light-sensitive diseases (eg, lupus, porphyria); ingestion of photosensitizingdrugs; hepatic disease; arsenic therapy; noncompliance or unwillingnessto use protective glasses after treatmentPregnancy

C - Fetal risk revealed in studies in animals but not established or notstudied in humans; may use if benefits outweigh risk to fetusPrecautions

Prolonged use with UV-A causes photoaging of skin; phototoxic reactions

possible; caution with hepatic insufficiency; eye protection necessaryduring and after therapy; use only if response to other therapy isinadequate; long-term use may increase risk of skin cancer

Trioxsalen (Trisoralen)

For treatment of hyperkeratosis. In UV-A radiation, inhibits mitosis bycovalently binding to pyrimidine bases in DNA.Adult

0.6-0.8 mg/kg PO with food 1.5 h prior to UV-A exposure once or twiceweekly; alternatively, 10 mg/d once 2-4 h before controlled exposure to

UV-A or sunlight; not to exceed 14 dPediatric

12 years: Administer as in adultsNone reportedDocumented hypersensitivity; a history of melanoma, acute lupuserythematosus, or porphyria; inability to comply with instructionsregarding UV-A exposure and eye protectionPregnancy

C - Fetal risk revealed in studies in animals but not established or notstudied in humans; may use if benefits outweigh risk to fetus


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Precautions

Prolonged use with UV-A causes photoaging of skin; severe burns mayoccur from sunlight or UV-A exposure if dose or frequency is exceeded;caution with hepatic insufficiency

Calcipotriene (Dovonex)Adult

Apply to affected areas bid (qam, qhs, and after washing); apply thin film,avoiding eyes and lips; do not cover with occlusive dressing.Pediatric

Not recommendedSubstances that stimulate absorption should not be administeredconcomitantly because of potential effects on calcium metabolismSystemic treatment of calcium deficiency; kidney or liver dysfunction;hypercalcemia or calcium metabolism problems

PregnancyC - Fetal risk revealed in studies in animals but not established or notstudied in humans; may use if benefits outweigh risk to fetusPrecautions

Breastfeeding not advised during treatment; low incidence of temporaryskin irritation (reddening, itching); temporarily or permanently discontinueor decrease frequency if sensitivity or severe irritation; in clinical studies,no hypercalcemia observed at maximal dose of 30 g/d

Immunomodulator

Tacrolimus (Protopic) ointment 0.03% or 0.1%

Adult

Apply to the affected area twice daily; continue for 1 wk after signs andsymptoms resolve. Avoid occlusive dressingsPediatric

Protopic 0.03% only: Apply as in adults

MiscellaneousMedicolegal Pitfalls

Physicians who prescribe PUVA therapy should be thoroughlyfamiliar with the risks of burns, cataract formation, andcarcinogenesis associated with treatment.

Patients should be made aware of signs and symptoms that suggestthe onset of hypothyroidism, diabetes, or other autoimmunediseases. If signs or symptoms occur, appropriate tests should beperformed.

Treatment must be individualized, and patients should be madeaware of the risks associated with therapy.

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